Amides of dibromo-and tribromomethanesulfonic acids

ABSTRACT

wherein   is a heterocyclic ring which may contain oxygen as another hetero atom and may be substituted with 1 to 2 lower alkyl groups, and x is 2 or 3. The compounds have antimicrobial activity. This invention concerns dibromo- and tribromomethanesulfonamides of the formula

United States Patent [191 Goralski July 1,1975

[ AMIDES OF DlBROMO-AND TRIBROMOMETHANESULFONIC ACIDS [75] Inventor: Christian T. Goralski, Midland,

Mich.

[73] Assignee: The Dow Chemical Company,

Midland, Mich.

221 Filed: Jan. 26, 1973 21 Appl. No.: 326,609

[52] US. Cl ..260/247.1R; 260/293.85;

260/326.85; 424/248; 424/267; 424/274 [51] Int. Cl.. C07d 27/04; C07d 29/34; C07d 47/86 [58] Field of Search 260/247.l, 293.85, 326.82

[56] References Cited FOREIGN PATENTS OR APPLICATIONS 940,128 10/l963 United Kingdom 260/556 A OTHER PUBLICATIONS Primary ExaminerLorraine A. Weinberger Assistant ExaminerMichael Shippen Attorney, Agent, or Firm-Theodore Post; C. Kenneth Bjork [57] ABSTRACT This invention concerns dibromoand tribromomethanesulfonamides' of the formula wherein is a heterocyclic ring which may contain oxygen as another hetero atom and may be substituted with l to 2 lower alkyl groups, and x is 2 or 3. The compounds have antimicrobial activity.

5 Claims, No Drawings 1 AMIDES OF DIBROMO-AND TRIBROMOMETHANESULFONIC ACIDS SUMMARY OF THE INVENTION This invention concerns dibromoand tribromome thanesulfonamides corresponding to the formula wherein R, and R together with the nitrogen atom form a heterocyclic group which contains up to one hetero oxygen atom and may be substituted with 1 to 2 lower alkyl groups, such as, for example, a pyrrolidinyl, piperidinyl, morpholinyl, 4-methylpiperidinyl, or a 2,6-dimethylmorpholinyl group and x represents 2 or 3. 1n the specification and claims, lower alkyl designates a l to 4 carbon atom straight or branched chain alkyl group, i.e., from 1, to 2, to 3, to 4 carbon atoms, such as, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl or secondary butyl. The compounds are prepared by reacting a diamide of sulfoacetic acid with a large excess of bromine (6 to 10 mols/mol of diamide) in the presence of an aqueous solution of an alkali metal hydroxide, preferably sodium or potassium hydroxide, for a period of from 1-48 hours, preferably 24-48 hours, filtering off the solid products, and sepa rating and purifying the products by fractional recrystallization from a suitable solvent, such as, for example, methanol or ethanol. The tribromomethanesulfonamides, being less soluble, crystallize out first; the dibromethanesulfonamides, being more soluble, crystallize second. The starting diamides of sulfoacetic acid may be prepared by the method of Hoogenboom et al., J. Org. Chem., 34, 3414 (1969).

DESCRIPTION OF SOME PREFERRED EMBODIMENTS The following examples describe representative specific embodiments and the best mode contemplated by the inventor of carrying out the invention. Tempera- EXAMPLE 1 In a 250 ml. single-neck flask equipped with a mag- 0 netic stirrer are placed 1.67 g. (0.005 mol) of 4-((2,6-

dimethylmorpholinosulfonyl)acetyl)-2,6-dimethylmorpholine, ml. of aqueous 20% sodium hydroxide solution, 100 ml. of water, and 4.80 g. (0.03 mol) of bromine. The reaction mixture is allowed to stir at room temperature for 46 hours, after which time a white solid separates which is shown by nuclear magnetic resonance spectroscopy to be a mixture of the dibromoand tribromotitle compounds. The solid is recrystallized from approximately 40 ml. of absolute ethanol to give 0.37 g. of crude 2,6-dimethyl-4- ((tribromomethyl )sulfonyl )morpholine. Recrystallization of this material from approximately 7 ml. of absolute ethanol gives, after vacuum drying, 0.20 g. of pure 2,6-dimethyl-4-((tribromomethyl)sulfonyl)morpholine, m.p. 183-184.5C.

Anal. Calcd. for C H Br NO S: C, 19.55; H, 2.81; N, 3.26; S, 7.45. Found: C, 19.82; H, 2.79; N, 3.27; S, 7.61.

The crystallization liquor from the isolation of the crude 2,6-dimethy1-4-((tribromomethy1)sulfonyl)morpholine is concentrated and cooled in a freezer to give 0.53 g. of crude 2,6-dimethyl-4-((dibromomethyl)sulfonyl)morpholine. Recrystallization of this material from approximately 7 ml. of absolute ethanol gives, after vacuum drying, 0.24 g. of pure 2,6-dimethyl-4- (dibromomethyl )sulfony1)morpholine, m.p. -108C.

Anal. Calcd. for C H Br NO S: C, 23.95; H, 3.73; N, 3.81; s, 9.15. Found: C, 23.61; H, 3.60; N, 3.81; S, 9.15.

EXAMPLE 2 Pursuant to the procedure of Example 1, the tri bromomethanesulfonamides given in the following Table are prepared.

Table I Amides of Tribromomethanesulfonic acid R 1 Br CSO N R Analysis Calcd Found R,R N Mp. C. C H S C H N S a. 200-202 17.92 3.01 3.48 7.98 17.65 3.00 3.46 not determined b. d N- 172 14.94 2.01 3.49 7.98 15.18 2.07 3.42 7.98

ture is given in Centigrade degrees. The compounds are 65 identified by elemental analysis and/or nuclear magnetic resonance spectroscopy.

The corresponding dibromo compounds are separated from the above compounds following the procedure of Example 1.

3 4 The compounds of the invention are employed as anfollowing Table presen t s resu'lts, expressed as concentimicrobials for the control of bacteria, fungi and tration of toxicant'in parts per million'to achieve 100% yeasts. For such uses, the compounds can be employed growth inhibition (kills) of the indicated organisms.

Table II Minimum Growth Inhibitory Concentration, ppm

Compound of Example Pa Sa Ca Tm 35 At Cp Pp St Mp Rn Ci Cf Ts l (a) 100 500 100 100 100 10 100 100 100 100 lOO 100 I 100 l (b) 500 500 500 500 500 500 500 2 (b) 100 500 100 100 100 100 lOO I00 100 I00 100 100 100 100 Pa P. ueruginosa S2: S. uureus Cu C. albicans Tm T. mentagrophyles B B. subtilis At A. terreus Cp C. pelliculosa Pp P. pullulans St S. lyphosa Mp M. phlei Rn R. nigricans Ci Ceratucystis ips Cf= Cephuloascus frugans Ts Trichoderm Sp. Madison P-42 not active at 500 ppm 50% control at 500 ppm in an unmodified form or dispersed on a finely divided What is claimed is: 1 solid and employed as dusts. Such mixtures can also be 1. A compound corresponding to the formula dis ersed in water with or without the aid of a surfacet p Br,H .,CSO NR,R A

active agent and the resulting aqueous suspensions employed as sprays. In other procedures, the products can wh i R and R together with the nitrogen atom be employed as active constituents in solvent solutions, f a h t lic ring of the group ofapyrrolidinyl,

oil-in-water or water-in-oil emulsions or aqueous disi idi l h fi l 4- h i jdi d persions. The augmented compositions are adapted to 2 i n h li l n X i or 3 be formulated as concentrates and subsequently di- 2 The compound ofclaim 1 which is 26 dimethyI 4 luted with additional liquidor solid adjuvants to pro- ((tribromomethynsulfonyl)morpholine t duce the ultimate treating compositions. Good results 3 The Compound of claim 1 whvichdis are obtained when employing compositions containing antimicrobial concentrations and usually from about 40 100 to 10,000 parts by weight of one or more of the ((tribromomethynsulfonyl)piperidine compounds per million parts of such composition. 5 The compound of claim w is In representative operations, compounds of the present invention were tested for their activity as anti- ((mbromomethy])sglfofyllmoafphf microbials using conventional agar dilution tests. The

4((dibromomethyl)sulfonyl)morpholine.-

4. The compound of claim 1 which is 1- 

1. A COMPOUND CORRESPONDING TO THE FORMULA
 2. The compound of claim 1 which is 2,6-dimethyl-4-((tribromomethyl)sulfonyl)morpholine.
 3. The compound of claim 1 which is 2,6-dimethyl-4((dibromomethyl)sulfonyl)morpholine.
 4. The compound of claim 1 which is 1-((tribromomethyl)sulfonyl)piperidine.
 5. The compound of claim 1 which is 4-((tribromomethyl)sulfonyl)morpholine. 